Abstract

The γ-aminobutyric acid_B(GABA_B) receptor was first demonstrated on presynaptic terminals where it serves as an autoreceptor and also as a heteroreceptor to influence transmitter release by suppressing neuronal Ca²⁺ conductance. Subsequent studies showed the presence of the receptor on postsynaptic neurones where activation produces an increase in membrane K⁺ conductance and associated neuronal hyperpolarization. (−)-Baclofen is a highly selective agonist for GABA_B receptors, whereas the established GABA_Areceptor antagonists, bicuculline and picrotoxin, do not block GABA_B receptors. The receptor is G_i/G_o protein-coupled with mixed effects on adenylate cyclase activity. The receptor comprises a heterodimer with similar subunits currently designated 1 and 2. These subunits are coupled via coiled-coil domains at their C termini. The evidence for splice variants is critically reviewed. Thus far, no unique pharmacological or functional properties have been assigned to either subunit or the variants. The emergence of high-affinity antagonists for GABA_B receptors has enabled a synaptic role to be established. However, the antagonists have generally failed to establish the existence of pharmacologically distinct receptor types within the GABA_B receptor class. The advent of GABA_B1 knockout mice has also failed to provide support for multiple receptor types.